Synthetic study of novel inositol phosphoceramide CJP2

新型神经节苷脂CJP2是由Higuchi及其同事从羽星Comanthus japonica中获得的。这种神经节苷脂的独特之处在于它是一种具有唾液酸的肌醇磷酸神经酰胺衍生物；这种神经节苷脂以前未被发现。9- o -甲基- n -糖基神经氨基基残基的存在在天然存在的神经节苷中也是独特的。肌醇磷酸神经酰胺（IPC）在高等植物、酵母、真菌、一些细菌培养物和突变酵母中存在相当数量。虽然它们的内源性功能尚不清楚，但它们被认为可以保护植物组织免受坏死损害，并有望作为组织浆菌病诊断的测试。由于CJP2的可用性有限，其生物活性尚不清楚。采用立体选择性全合成d -葡萄糖的方法研究了提供这类化合物的充分合成方法。IPC肌醇片段的合成主要通过乙烯基铜试剂在d -葡萄糖衍生的手性醛上的非对映选择性1,2加成、Wittig甲基化、1,7-二烯的闭合环复分解（RCM）和催化非对映选择性OsO4二羟基化反应进行。根据小川法的改进步骤合成了神经酰胺片段。以d -葡萄糖为原料合成了唾液酸衍生物的糖基片段，作为唾液酸糖基供体的有用前体。该合成的关键步骤是1,7-二烯通过RCM直接形成不饱和糖基，生成唾液酸糖基衍生物。本实验合成了CJP2的肌醇片段、神经酰胺片段和唾液酸糖基片段。这些片段的进一步官能团转化和偶联将为CJP2及其相关类似物提供有价值的生物学评价。

The novel type ganglioside CJP2 has been obtained by Higuchi and co-workers from the feather star Comanthus japonica. This ganglioside is unique in that it is an inositolphosphoceramide derivative possessing sialic acid ; such ganglioside has not previously been identified. The presence of 9-O-methyl-N-glycolylneuraminosyl residue is also unique in naturally occurring gangliosides. Inositol phosphoceramide (IPC) is present in quite considerable quantities in higher plants, yeast, fungi, some bacterial cultures and mutant yeasts. Though their endogeinc functions are not well understood, but they are believed to protect plant tissues from necrotic lesions and are supposed to be applicable as test for the diagnosis of histoplasmosis. Because of limited availability of CJP2, their biological activity remains unknown. Development of the sufficient synthetic method to supply this class of compounds was investigated by stereoselective total synthesis from D-glucose. The synthesis of myo-inositol fragment of IPC is characterized by diastereoselective 1,2-addition of vinyl copper reagent to the chiral aldehyde derived from D-glucose, Wittig metbylenation, Ring-closing metathesis (RCM) of 1,7-diene and catalytic diastereoselective OsO4 dihydroXylation. The ceramide fragment was synthesized according to the modified procedure of Ogawa's method. The glycal fragment of sialc acid derivative as the useful precursor of glycosyl donor of sialic acid was also synthesized from D-glucose. The key step of this synthesis is the direct formation of unsaturated glycal moiety by RCM of 1,7-diene to produce sialic acid glycal derivative. The present synthesis provided myo-inositol fragment, ceramide fragment and sialic acid glycal fragment of CJP2. Further functional group transformation and coupling of these fragments will provide CJP2 and its related analogs valuable for biological evaluations.